Locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) MedDRA version: 21.0 Level: PT Classification code 10041823 Term: Squamous cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
InflaRx GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years of age on day of signing informed consent 2. Patients with biopsy-proven, histologically or cytologically confirmed (a) locally advanced cSCC not amenable for curative treatment or (b) metastatic cSCC. Patients must have been treated with all approved therapies for (a.) inoperable locally advanced cSCC contraindicated for radiation therapy or (b.) metastatic cSCC. All patients to be include must have progressed on PD-1- or PD-L1 inhibitory antibody therapy. 3. Patients must have progressed on treatment with an anti PD1/L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD 1 treatment progression is defined by meeting all of the following criteria: a) Has received =2 doses of an anti-PD-1/L1 mAb that has been approved for treatment of cSCC or any solid tumor b) Has demonstrated progressive disease (PD)/confirmed PD (iCPD) after PD-1/L1 inhibitor treatment as defined by modified response evaluation criteria in solid tumors (RECIST) version 1.1/RECIST for immune-base therapeutics (iRECIST). The initial evidence of PD is to be confirmed by a second assessment =4 weeks from the date of the first documented PD, unless there is rapid clinical progression. c) Disease progression has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. 4. The PD-1-/PD-L1 infusion must have been the most recent treatment for locally advanced or metastatic cSCC. 5. Patients must consent to undergo the following biopsies (at each time point a punch biopsy of externally visible cSCC lesions or a biopsy of material from accessible metastases) for biomarker assessments: a) At baseline, prior to the first administration of the investigational therapy and if possible, within 7 days prior to initiation of study treatment administration (mandatory for all patients) b) For Stage 2 patients only: on Cycle 2 Day 1 (±3 days) (mandatory) c) For Stage 2 patients only: at the time of CR/iCR/PR/iPR (optional, to be conducted only if the investigator considers this biopsy as clinically possible and potentially informative) d) For Stage 2 patients only: At the time of tumor progression (optional, to be conducted only if the investigator considers this biopsy as clinically possible and potentially informative). For all biopsies intended to analyze biomarkers, it is important to obtain sufficient material to conduct the biomarker program, which needs to be the equivalent to a 4 mm x 4 mm punch biopsy. If biopsies for biomarkers are not feasible due to the complete absence of any suitable cutaneous or metastatic lesions, then this is not an exclusion criterium. However, this needs to be documented and confirmed by the investigator. The biopsied lesion is not considered a target lesion. 6. Patients must have the following minimum washout before first study treatment administration from previous treatments: • =4 weeks for mAbs, systemic cytotoxic anticancer therapy, treatment with other anticancer investigational agents • =3 weeks for local radiation therapy Note: Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system disease. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) status of =1 8. Adequate organ function: Hematological: Absolute neutrophil co
Exclusion criteria
Exclusion criteria: 1. Patients with limited cSCC, who do not require systemic therapy 2. Has known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for =4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for =14 days prior to first dose of study treatment. 3. Has a diagnosis of immunodeficiency or autoimmune disease, or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 3 weeks prior the first dose of study treatment 4. Patients who have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis 5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen 4, OX 40, CD137) and was discontinued from that treatment due to a =Grade 3 immune-related adverse event (irAE) 6. Has severe hypersensitivity (=Grade 3) to pembrolizumab or IFX-1 and/or any of their excipients or had a severe (=Grade 3) infusion-related reaction to treatments with other mAbs 7. Patients who fulfil inclusion criterion 6 (washout times) but who have not recovered from side effects of such therapies 8. Has received a live vaccine within 30 days prior to the first dose of study treatment 9. Patients who have undergone major surgery <4 weeks prior to starting study treatment 10. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. 11. Patients with known =Grade 3 (per National Cancer Institute common terminology criteria for adverse events [NCI CTCAE] v5.0 criteria) active systemic or cutaneous viral, bacterial, or fungal infection 12. Patients with known history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. 13. Patients who have a history of human immunodeficiency virus infection 14. Patients who have a history of interstitial lung disease 15. Patients who have had an allogeneic tissue/solid organ transplant 16. Patients with a history of other malignancies during the past 5 years. Note: The following are exempt from the 5-year limit: curatively resected basal cell carcinoma, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy. 17. Patients who are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 3 months after the last dose of IFX-1 or 120 days after the last dose of pembrolizumab 18. Women of childbearing potential (WOCBP) who have a positive serum pregnancy test result within 7 days before treatment. Note: Post-menopausal women must be amenorrheic for =12 months to be considered not WOCBP. 19. Male patients and WOCBP who do not agree
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Arm A: • To assess the antitumor activity of IFX-1 Arm B: • To determine the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) • To assess the antitumor activity of IFX-1 + pembrolizumab • To assess the safety profile of IFX-1 + pembrolizumab;Secondary Objective: Arm A: • To further assess efficacy of IFX-1 • To assess the safety profile of IFX-1 • To assess the pharmacokinetics (PK) of IFX-1 • To monitor the immunogenicity of IFX-1 • To assess the impact of IFX-1 on quality of life (QoL) Arm B: • To further assess efficacy of IFX-1 • To assess the PK of IFX-1 • To monitor the immunogenicity of IFX-1 • To assess the impact of IFX-1 + pembrolizumab on QoL;Primary end point(s): Arm A: • Investigator assessed best overall response rate (ORR) for IFX-1, with response being defined as best response of CR/confirmed CR (iCR) or PR/confirmed PR (iPR) per modified RECIST v1.1/iRECIST. Arm B: • Frequency of dose-limiting toxicities (DLTs) by dose cohort • Investigator assessed best ORR per modified RECIST v1.1/iRECIST for IFX-1 + pembrolizumab • Frequency, severity, and investigational new drug (IND) attribution of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) according to Medical Dictionary for Regulatory Activities (MedDRA) coding (version valid at time of reporting) and the NCI CTCAE grading system (version 5.0, 27 November 2017);Timepoint(s) of evaluation of this end point: Every 6 weeks for disease assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Arm A: • Response (CR/iCR/PR/iPR) and stable disease (SD) duration • Disease control rate (CR/iCR+PR/iPR+SD) • Progression-free survival (PFS) • Overall survival (OS) • Frequency, severity, and IND attribution of TEAEs and SAEs according to MedDRA coding (version valid at time of reporting) and the NCI CTCAE grading system v5.0 • Maximum (Cmax) and trough concentration (Ctrough) of IFX-1, and concentration at the infusion end (Clast) • Area under the IFX-1 concentration time curve from Time 0 to Day 4 (AUC0-day4) and Time 0 to Day 8 (AUC0-day8) • Development of human antidrug antibodies (ADAs) against IFX-1 • Changes in QoL as per the European Organisation for Research and Treatment of Cancer (EORTC)-QoL questionnaire (QLQ)-C30 total score Arm B: • Response (CR/iCR/PR/iPR) and SD duration • Disease control rate (CR/iCR+PR/iPR+SD) • PFS • OS • Cmax, Ctrough, and Clast of IFX-1 • AUC0-day4 and AUC0-day8 for IFX-1 • Development of human ADAs against IFX-1 • Changes in QoL as per the EORTC-QLQ-C30 total score;Timepoint(s) of evaluation of this end point: Every 6 weeks for disease assessment. In between timepoints depending on central lab sampling/analysis, QoL questionnaires and SAE monitoring. | — |
Countries
Belgium, France, Germany, Spain, United States
Contacts
Public ContactSenior Director, Clinical Research
InflaRx GmbH
Outcome results
None listed